Aerosol formulation containing an ester-, amide-, or mercaptoester-derived dispersing aid

A medicinal aerosol formulation containing a particulate drug and a dispersing aid derived from a hydroxyacid, a mercapto acid, or an amino acid.

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Claims

1. A metered dose inhaler containing a medicinal aerosol formulation, the formulation comprising:

(i) a dispersing aid comprising a compound comprising a chain of units derived from a precursor selected from the group consisting of a hydroxyacid, an amino acid, a mercapto acid, and a combination of any two or more of the foregoing;
(ii) a propellant; and
(iii) a therapeutically effective amount of a particulate drug, wherein the formulation is substantially readily redispersible and upon redispersion does not flocculate, cream, or settle so quickly as to prevent reproducible dosing of the drug.

2. A metered dose inhaler according to claim 1, wherein the chain of the formulation is capped on at least one end by a group that contains no hydrogen atoms capable of hydrogen bonding.

3. A metered dose inhaler according to claim 1, wherein the chain of the formulation is bonded at least one end to a moiety that contains an ionic group.

4. A metered dose inhaler according to claim 1, wherein the chain of the formulation is bonded at least one end to a moiety that contains a group that contains one or more hydrogen atoms capable of hydrogen bonding.

5. A metered dose inhaler according to claim 1, wherein the dispersing aid comprises a chain comprising units derived from one or more hydroxyacids.

6. A metered dose inhaler according to claim 1, wherein the chain of the formulation comprises units derived from a precursor selected from the group consisting of glycolic acid, trimethylene carbonate, hydroxybutyric acid, p-dixanone, and lactic acid.

7. A metered dose inhaler according to claim 1, wherein the chain of the formulation comprises units derived from L-lactic acid.

8. A metered dose inhaler according to claim 1, wherein the dispersing aid comprises a chain comprising units derived from one or more amino acids.

9. A metered dose inhaler according to claim 1, wherein the dispersing aid comprises a chain comprising units derived from one or more mercapto acids.

10. A metered dose inhaler according to claim 1, wherein the formulation comprises a mixture of a first dispersing aid and a second dispersing aid.

11. A metered dose inhaler containing a medicinal aerosol formulation, the formulation comprising:

(i) a dispersing aid comprising a compound comprising a chain of units of the formula ##STR11## wherein each R.sub.1 is an independently selected organic moiety that links the -x-group to the carbonyl group, and X is --O--, --S--, or catenary nitrogen;
(ii) a propellant; and
(iii) a therapeutically effect amount of a particulate drug;

12. A metered dose inhaler according to claim 11, wherein the chain of the formulation contains less than about 100 of said units.

13. A metered dose inhaler according to claim 11, wherein the chain of the formulation contains between about 3 and about 70 of said units.

14. A metered dose inhaler according to claim 11, wherein the chain of the formulation contains between about 3 and about 14 of said units.

15. A metered dose inhaler according to claim 11, wherein R.sub.1 is straight chain, branched chain, or cyclic alkylene or alkenylene, optionally containing carbonyl, oxy, thio, or catenary nitrogen, arylene or arylene substituted by non-nucleophilic or non-hydrogen donor hydrogen bonding functional groups, or a combination of such arylene, alkenylene, and alkylene groups.

16. A metered dose inhaler according to claim 11, wherein --X-- is catenary fully substituted nitrogen wherein the substituent is a group that is free of nucleophilic or hydrogen-donor hydrogen bonding functional groups.

17. A metered dose inhaler according to claim 11, wherein the carbonyl end of the chain is bonded to an.alpha.-amino acid residue of the formula ##STR12## wherein R.sub.3 is hydrogen and R.sub.4 is straight chain, branched chain, or cyclic alkylene containing one catenary carbon atom and a total of one to about 12 carbon atoms, optionally substituted by one or more of lower alkoxy, lower alkylthio, carboxy, mercapto, hydroxy, phenyl, hydroxyphenyl, indolyl, guanidinyl, carbamido, imidazolyl, or acylamino, or wherein R.sub.3 and R.sub.4 together form a butane-1,1,4-triyl group optionally substituted by hydroxy.

18. A metered dose inhaler according to claim 17, wherein the carbonyl end of the chain is bonded to a group derived from taurine.

19. A metered dose inhaler according to claim 17, wherein the chain comprises units of the formula --OCH(CH.sub.3)C(O)--.

Referenced Cited
U.S. Patent Documents
2362511 November 1944 Teeters
2733252 January 1956 Thompson et al.
2789992 April 1957 Thompson et al.
3098795 July 1963 Kreps
3728447 April 1973 Osipow et al.
3933825 January 20, 1976 Fiscella et al.
4029606 June 14, 1977 Isa et al.
4846991 July 11, 1989 Suzue et al.
4948583 August 14, 1990 Grollier et al.
5008028 April 16, 1991 Jolley et al.
5126123 June 30, 1992 Johnson
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Foreign Patent Documents
521455 A2 January 1993 EPX
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666406 A5 July 1988 CHX
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92/00062 January 1992 WOX
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Other references
  • Polymer Preprints, Japan (English Edition), vol. 41, No. 5-11, p. 1681. JP 04169554 A (Derwent Abstract). JP 04198394 A (Derwent Abstract). Chemical Abstracts 117(14):134300a (Fujii, Mar. 1992). Chemical Abstracts 117(14):134337h (Nakahara, Mar. 1992). Chemical Abstracts 117(14):134340d (Tanaka, Mar. 1992). Chemical Abstracts 117(24):237045r (Nakahara, May 1992). Chemical Abstracts 117(24):237046s(Nakahara, May 1992). Chemical Abstracts 117(26):254711x (Fujii, Jun. 1992). Chemical Abstracts 118(4):24870q (Fujii, Jun. 1992). Chemical Abstracts 118(8):62799f (Lache, 1991). Chemical Abstracts 118(12):106175f (Nakahara, Nov. 1992).
Patent History
Patent number: 5725841
Type: Grant
Filed: Oct 28, 1996
Date of Patent: Mar 10, 1998
Assignee: Minnesota Mining and Manufacturing Company (St. Paul, MN)
Inventors: Daniel C. Duan (St. Paul, MN), James S. Stefely (Woodbury, MN), David W. Schultz (Pine Springs, MN), Chester L. Leach (Lake Elmo, MN)
Primary Examiner: Carlos A. Azpuru
Attorneys: Gary L. Griswold, Walter N. Kirn, Ted K. Ringsred
Application Number: 8/738,519